Survivors of acute respiratory distress syndrome/acute lung injury (ALI) commonly experience significant and persistent neuromuscular weakness and impaired physical function, but little is known about the etiology, treatment and prevention of this important complication. Neuromuscular dysfunction acquired in the intensive care unit (ICU) is common, but has not been systematically studied in ALI patients, and its association with weakness and physical function has not been rigorously evaluated. Our overall goal is to improve ICU survivors' physical function, and through this research, we will conduct relevant and rigorous clinical investigations of ICU-acquired neuromuscular dysfunction. Hypotheses and specific aims. We hypothesize that ICU-acquired neuromuscular dysfunction is common in ALI patients, affected by ICU nutritional and pharmacologic interventions, and associated with short- and long-term impairment of physical function. Our aims are: (1) to determine the incidence of ICU- acquired neuromuscular dysfunction in ALI; (2) to investigate the relationship between ARDS Network randomized trial interventions and development of this dysfunction, and (3) to assess the association of ICU- acquired neuromuscular dysfunction with short- and long-term neuromuscular weakness and physical function. Study design and methods. We propose a prospective longitudinal cohort study of 270 patients enrolled in ARDS Network randomized trials at 4 study sites. We will identify ICU-acquired neuromuscular dysfunction using electrophysiologic assessments performed at study entry and weekly thereafter while in the ICU. Incidence will be measured as the proportion of subjects with ICU-acquired neuromuscular dysfunction (myopathic and/or neuropathic) detected at any time in the ICU. We will investigate the effect of ARDS Network interventions by comparing the incidence of dysfunction at study day 7 between randomized treatment groups. We will assess the association of neuromuscular dysfunction with short- and long-term weakness and physical function via standardized clinical evaluations before hospital discharge and at 6 and 12 months after ALI onset. Significance. This research addresses three critical gaps in scientific knowledge regarding the epidemiology, effect of experimental therapies, and long-term consequences of ICU-acquired neuromuscular dysfunction in ALI patients. Data from this study are essential to build the foundation of knowledge necessary to improve the serious short- and long-term sequelae commonly experienced by ALI survivors. PUBLIC HEALTH RELEVANCE: Since patients in the intensive care unit (ICU) frequently have acute muscle and nerve dysfunction, and persistent weakness and impaired quality of life after hospital discharge, new research is urgently required to understand these short and long-term morbidities. We will study ICU-acquired neuromuscular dysfunction in a subset of patients with acute lung injury (ALI) who are enrolled in National Heart Lung and Blood Institute-funded clinical trials. In studying ICU-acquired neuromuscular dysfunction, our aims are: (1) to systematically measure its incidence within the ALI trials; (2) to evaluate if the treatments tested in the trials affect its incidence; and (3) to investigate its association with longer-term physical function.